Evolution of Nova-Dependent Splicing Regulation in the Brain 英文参考文献.docVIP

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Evolution of Nova-Dependent Splicing Regulation in the Brain 英文参考文献.doc

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Evolution of Nova-Dependent Splicing Regulation in the Brain 英文参考文献

EvolutionofNova-Dependent SplicingRegulationintheBrain Nejc Jelen1,2,3,4[,Jernej Ule3[*,Marko Zivinˇ 4,Robert B.Darnell1,2 1LaboratoryofMolecularNeuro-Oncology,TheRockefellerUniversity,NewYork,NewYork,UnitedStatesofAmerica,2HowardHughesMedicalInstitute,TheRockefeller University, New York, New York, United States of America, 3 Division of Structural Studies, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom, 4 Brain ResearchLaboratory,InstituteofPathophysiology,UniversityofLjubljana,Ljubljana,Slovenia A large number of alternative exons are spliced with tissue-specific patterns, but little is known about how such patternshaveevolved.Here,westudytheconservationoftheneuron-specificsplicingfactorsNova1andNova2andof thealternativelysplicedexonstheyregulateinmousebrain.WhereasNovaRNAbindingdomainsare94%identical acrossvertebratespecies,Nova-dependentsplicingsilencerandenhancerelements(YCAYclusters)showmuchgreater divergence,aslessthan50%ofmouseYCAYclustersareconservedatorthologouspositionsinthezebrafishgenome. To study the relation between the evolution of tissue-specific splicing and YCAY clusters, we compared the brain- specific splicing of Nova-regulated exons in zebrafish, chicken, and mouse. The presence of YCAY clusters in lower vertebratesinvariablypredictedconservationofbrain-specificsplicingacrossspecies,whereastheirabsenceinlower vertebratescorrelatedwithalossofalternativesplicing.WehypothesizethatevolutionofNova-regulatedsplicingin highervertebratesproceedsmainlythroughchangesincis-actingelements,thattissue-specificsplicingmightinsome casesevolveinasinglestepcorrespondingtoevolutionofaYCAYcluster,andthattheconservationlevelofYCAY clustersrelatestothefunctionsencodedbytheregulatedRNAs. Citation:JelenN,UleJ,ZˇivinM,DarnellRB(2007)EvolutionofNova-DependentSplicingRegulationintheBrain.PLoSGenet3(10):e173.doi:10.1371/journal.pgen.0030173 and frame preservation relative to other alternative exons [16,17]. Introduction Alternative splicing is belie